Peanut agglutinin, a lectin with an unusual quaternary structure and interesting ligand binding properties

Abstract

Lectins are multivalent proteins which play their biological role through the ability to specifically bind different carbohydrate structures. This ability has also led to their myriad applications. They occur in all forms of life. Among plant lectins, those from leguminous plants constitute the most thoroughly studied family. Most of the well-characterized legume lectins can be classified as mannose (Man)/glucose (Glc) specific or galactose (Gal)/N-acetylgalactosamine (GalNAc) specific. Tetrameric, non-glycosylated peanut agglutinin (PNA) is the most thoroughly investigated member of the Gal/GalNAc specific family of legume lectins. Its structure indicated that open quaternary association also needed to be considered when dealing with multimeric proteins. The structure also helped to establish legume lectins as a family of proteins in which small alterations in essentially the same tertiary structure lead to large changes in quaternary association. It provides an explanation for the exclusive specificity of PNA for galactose at the primary site. The structures of the relevant complexes demonstrated that the specificity of the lectin for T-antigen at the disaccharide level is caused by a water-bridge, thus establishing water-mediated interactions as a strategy for generating ligand specificity. In disaccharide complexes, the second residue interacts directly with the protein only when the glycosidic linkage is β1-3 or β1-4. Studies on the interactions of PNA with a bivalent ligand provide valuable insights into the multivalency of lectins. The availability of detailed structural information on the lectin permitted rational re-design of its combining site. A comparison of the available structural data on PNA led to the elucidation of the limited plasticity of the lectin molecule and its relation to function. An exploration of its hydration shell brought out the importance of conserved water molecules in the structure and function of PNA. Interestingly, while the Man/Glc specific concanavalin A, the most thoroughly studied lectin to date, represents the conventional wisdom on legume lectins, PNA, perhaps the next most extensively studied legume lectin, largely highlights departures from it.